Genetic Variant NM_207309.3:c.164A>C (chr9-137077696-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_207309.3(UAP1L1):c.164A>C(p.Glu55Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000376 in 1,143,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

UAP1L1
NM_207309.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.474

Variant links:

Genes affected

UAP1L1 (HGNC:28082): (UDP-N-acetylglucosamine pyrophosphorylase 1 like 1) Predicted to enable UDP-N-acetylglucosamine diphosphorylase activity. Predicted to be involved in UDP-N-acetylglucosamine biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

UAP1L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050865173).

BP6

Variant 9-137077696-A-C is Benign according to our data. Variant chr9-137077696-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2349070.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UAP1L1	NM_207309.3 link	c.164A>C	p.Glu55Ala	missense_variant	Exon 1 of 9	ENST00000409858.8	NP_997192.2	Q3KQV9-1
UAP1L1	XM_047424066.1 link	c.164A>C	p.Glu55Ala	missense_variant	Exon 1 of 8		XP_047280022.1
UAP1L1	XM_006717317.4 link	c.164A>C	p.Glu55Ala	missense_variant	Exon 1 of 8		XP_006717380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UAP1L1	ENST00000409858.8 link	c.164A>C	p.Glu55Ala	missense_variant	Exon 1 of 9	1	NM_207309.3	ENSP00000386935.3		Q3KQV9-1
UAP1L1	ENST00000476184.5 link	n.164A>C		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000484649.1		A0A087X226

Frequencies

GnomAD3 genomes

AF:

0.0000539

AC:

AN:

148414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000134

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0000300

Gnomad OTH

AF:

0.000490

GnomAD4 exome

AF:

0.0000352

AC:

AN:

995060

Hom.:

Cov.:

AF XY:

0.0000341

AC XY:

AN XY:

469078

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000711

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000254

Gnomad4 OTH exome

AF:

0.000107

GnomAD4 genome

AF:

0.0000539

AC:

AN:

148524

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

72432

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000134

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000300

Gnomad4 OTH

AF:

0.000484

Bravo

AF:

0.0000793

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 06, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.6

DANN

Benign

0.64

DEOGEN2

Benign

0.0084

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.60

M_CAP

Benign

0.030

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.4

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.70

REVEL

Benign

0.059

Sift

Benign

0.69

Sift4G

Benign

0.71

Polyphen

0.0

Vest4

0.10

MutPred

0.56

Gain of MoRF binding (P = 0.0622);

MVP

0.030

MPC

0.26

ClinPred

0.028

GERP RS

-0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.045

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over